Changes in Na(+)-K(+)-ATPase activity influence cell attachment to fibronectin

Am J Physiol Cell Physiol. 2002 Feb;282(2):C302-9. doi: 10.1152/ajpcell.00117.2001.


Most vital cellular functions are dependent on a fine-tuned regulation of intracellular ion homeostasis. Here we have demonstrated, using COS cells that were untransfected or transfected with wild-type rat ouabain-resistant Na(+)-K(+)-ATPase, that partial inhibition of Na(+)-K(+)-ATPase has a dramatic influence on cell attachment to fibronectin. Ouabain dose-dependently decreased attachment in untransfected cells and in cells expressing wild-type Na(+)-K(+)-ATPase, but not in cells expressing ouabain-insensitive Na(+)-K(+)-ATPase, whereas inhibition of Na(+)-K(+)-ATPase by lowering extracellular K(+) concentration decreased attachment in all three cell types. Thirty percent inhibition of Na(+)-K(+)-ATPase significantly attenuated attachment. Na(+)-K(+)-ATPase inhibition caused a sustained increase in the intracellular Ca(2+) concentration that obscured Ca(2+) transients observed in untreated cells during attachment. Inhibitors of Ca(2+) transporters significantly decreased attachment, but inhibition of Na(+)/H(+) exchanger did not. Ouabain reduced focal adhesion kinase autophosphorylation but had no effect on cell surface integrin expression. These results suggest that the level of Na(+)-K(+)-ATPase activity strongly influences cell attachment, possibly by an effect on intracellular Ca(2+).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Calcium / metabolism
  • Calcium-Binding Proteins / antagonists & inhibitors
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Physiological Phenomena*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Extracellular Space / metabolism
  • Fibronectins / physiology*
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Intracellular Membranes / metabolism
  • Ouabain / pharmacology
  • Phosphorylation / drug effects
  • Potassium / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Rats
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Calcium-Binding Proteins
  • Enzyme Inhibitors
  • Fibronectins
  • Ouabain
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Ptk2 protein, rat
  • Sodium-Potassium-Exchanging ATPase
  • Potassium
  • Calcium